
DOI . ORG {
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Title[redir]:
Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro | Digestive Diseases and Sciences
Description:
Background We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. Aim To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. Methods and Results In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation. Conclusions This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.
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Keywords {🔍}
dht, cell, cells, pubmed, oear, expression, article, cancer, androgen, google, scholar, proliferation, eac, lines, fkbp, cas, coculture, direct, fig, vehicle, growth, myofibroblasts, androgenresponsive, arexpressing, receptor, prostate, monoculture, days, effect, supplementary, gene, fibroblasts, genes, medium, central, human, signaling, adenocarcinoma, vitro, measured, induced, concentrations, inhibition, single, nuclear, daily, data, pshtert, jhar, esophageal,
Topics {✒️}
ar/beta-catenin/tcf-4 complex inhibition article download pdf full size image phenol red-free rmpi-1640 sfg-rfp/rluc construct sa-β-gal stained cells gastro-esophageal reflux disease ar-expressing cell lines ar ligand 5α-dihydrotestosterone lab-tek chamber slides 25 μg/ml propidium iodide time-lapse confocal microscopy androgen-responsive gene fkbp5 ar-expressing cells induced androgen-responsive gene expression ar-expressing eac cells ar-negative cell lines androgen-responsive genes fkbp5 van der schoor dht dose-dependent alteration androgen-depleted growth medium ar-transduced cell line androgen-induced growth inhibition human prostate cancer c-myc transcription androgen-independent disease privacy choices/manage cookies extensive cell death ar-expressing lines dht dose-dependent distribution 5α-dihydrotestosterone eac primary cellular component proliferation dose–response curves androgen receptors eac cell lines induce cell death sa-β-gal breast cancer development human thyroid papillary cell cycle arrest dht dose–response curves cancer cell lines nuclear receptors green fluorescent protein european economic area hospital research foundation translational health research prostate cancer outcome adenocarcinoma cell line inhibit oe33-ar growth
Questions {❓}
- Androgens and esophageal cancer: what do we know?
- Androgens in endometrial carcinoma: the killer or helper?
- Oesophageal adenocarcinoma: the new epidemic in men?
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headline:Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro
description:We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation. This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.
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Esophageal adenocarcinoma
Androgen receptor
Fibroblast
FKBP5
Dihydrotestosterone
Direct co-culture
In vitro
Gastroenterology
Hepatology
Oncology
Transplant Surgery
Biochemistry
general
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headline:Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro
description:We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation. This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.
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dateModified:2017-10-20T00:00:00Z
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Esophageal adenocarcinoma
Androgen receptor
Fibroblast
FKBP5
Dihydrotestosterone
Direct co-culture
In vitro
Gastroenterology
Hepatology
Oncology
Transplant Surgery
Biochemistry
general
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